Certain medical treatments involve inserting a tube, such as a catheter, a needle, a cannula, an endoscope, etc., into a patient (e.g., a human or animal subject) and delivering a therapeutic agent to the patient via the tube. In some cases, the tube delivers the therapeutic agent for a systemic impact. For example, the therapeutic agent disperses throughout the patient's body to treat a disease likewise spread throughout the patient's body. In other cases, the tube delivers the therapeutic agent to a specific site that is diseased or that may otherwise need treatment. For example, such a site might be a diseased area of a heart, an artery, a vein, a lesion, or cardiovascular tissue that is ischemic or necrotic. In such instance, a practitioner positions the distal tip of the tube at the treatment site, for example at an area of the patient's heart, and injects a therapeutic agent into the proximal end of the tube located outside of the body. The therapeutic agent flows through the tube and into the target tissue. In other words, conventional catheters deliver therapeutic agents over a channel that extends from the proximal catheter end to the distal catheter end.
This conventional approach subjects the therapeutic agent to mechanical stress (e.g., shear stress) and other conditions that may be problematic as the agent flows through the catheter channel. While many conventional therapeutic agents are mechanically robust and can withstand such stress, cells (such as stem cells), certain particles, and certain other therapeutic agents (and potentially certain large molecule drugs) are sensitive to stress, and their therapeutic effectiveness can be impaired during flow through the channel. Studies show that these agents, unlike typical traditional therapeutic agents, can be affected in complex ways by biomechanical forces and environmental factors typically associated with their handling and, more significantly, with their delivery to an organ, organs or organ system(s) in need of treatment. Although these effects can dramatically influence therapeutic agent efficacy, insufficient attention has been paid to managing adverse forces and conditions incurred during delivery.
Delivery over a long catheter channel can cause problems even when shear stress is modest. A modest but sustained shear stress can subject a therapeutic agent to a significant, detrimental shear dose, for example. The term “shear dosing,” as used herein, generally refers to the magnitude of shear (or shear stress or a related parameter) to which an agent is subjected, integrated over time of exposure. (For example, a shear dose may be computed as an integral of shear over time.) A catheter having a long delivery channel that subjects a therapeutic agent to modest shear over an extended period of time may produce a high shear dose that compromises therapeutic efficacy. Likewise, the impact of conditions other than shear can accumulate as an agent flows along an extended catheter channel.